CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages.
CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages.
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DOI：
10.3389/fimmu.2021.635267
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang XW
中科院分区：
文献类型：
--
作者：
Gu Y;Hu X;Ge PB;Chen Y;Wu S;Zhang XW
CTRP1 （C1q/TNF-α[肿瘤坏死因子-α]相关蛋白1）是一种脂联素类似物，与糖尿病和心血管疾病的不良事件相关。然而，其对心肌梗死后心功能的影响尚不清楚。我们的研究旨在探讨CTRP1在心肌梗死后心功能中的作用，采用左前降结扎术对CTRP1基因全敲除小鼠进行心肌梗死模型的建立。C57BL6J小鼠在心肌梗死后第7天给予重组CTRP1蛋白（200 μg/kg），结果显示，心肌梗死后第4周，CTRP1缺乏小鼠的存活率增加，梗死面积减少，心功能改善，炎症和氧化应激水平降低，而注射CRTP1的小鼠病情恶化。然而，在缺氧条件下，与对照组相比，CTRP1沉默或CTRP1治疗的心肌细胞在炎症和氧化应激水平上几乎没有差异。在干扰素-γ的作用下，CTRP1缺失小鼠巨噬细胞的活化降低，而CTRP1增强了巨噬细胞对干扰素-γ的活化。巨噬细胞清除剂和氯膦酸脂质体可拮抗小鼠CTRP1注射的作用。我们还发现CTRP1通过脂联素受体1调节巨噬细胞的激活，脂联素受体1与巨噬细胞膜上的TLR4结合。TLR4敲除还能拮抗CTRP1蛋白对心肌梗死小鼠的作用。综上所述，这些数据表明，CTRP1通过TLR4对巨噬细胞抑制心肌梗死后的心功能。靶向CTRP1可能成为心肌梗死后心功能障碍的治疗方法。
CTRP1 (C1q/TNF-α [tumour necrosis factor-α]-related protein 1), an adiponectin paralog, is associated with diabetes and adverse events in cardiovascular disease. However, its effect on cardiac function post myocardial infarction (MI) is unclear. Our study aimed to explore the role of CTRP1 in cardiac function post MI. CTRP1 global knockout mice were subjected to left anterior descending ligation to establish the MI model. C57BL6J mice were also administered recombinant CTRP1 protein (200 μg/kg) 7 days post MI. As a result, mice with CTRP1 deficiency exhibited an increased survival rate, a reduced infarct area, improved cardiac function and decreased inflammation and oxidative stress levels at 4 weeks post MI compared with those of mice receiving the CRTP1 injection, whose conditions deteriorated. However, cardiomyocytes with either CTRP1 silencing or CTRP1 treatment showed few differences in inflammation and oxidative stress levels compared with those of the control under hypoxic conditions. The activation of macrophages isolated from CTRP1-deficient mice was decreased in response to interferon-γ, while CTRP1 enhanced the activation of macrophages in response to interferon-γ. Macrophage scavengers and clodronate liposomes antagonized the effects of CTRP1 injection in mice. We also found that CTRP1 regulated macrophage activation via adiponectin receptor 1, which binds to TLR4 on the macrophage membrane. TLR4 knockout also antagonized the effects of the CTRP1 protein on mice with MI. Taken together, these data indicate that CTRP1 supresses cardiac function post MI via TLR4 on macrophages. Targeting CTRP1 may become a promising therapeutic approach to cardiac dysfunction post MI.
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影响因子：
3.7
作者：
Avlas O;Bragg A;Fuks A;Nicholson JD;Farkash A;Porat E;Aravot D;Levy-Drummer RS;Cohen C;Shainberg A;Arad M;Hochhauser E
通讯作者：
Hochhauser E
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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